Later On

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The Secret Power of the Cell’s Waste Bin

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Esther Landhuis writes in Quanta:

At a conference in Maine during the summer of 2008, the biochemist David Sabatini stood before an audience of his peers, prepared to dazzle them with a preview of unpublished results emerging from his lab at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. The presentation did not go over well. His group was studying mTOR, a cellular enzyme he and colleagues had discovered more than a decade earlier. Among other things, they had tried to find out where mTOR aggregates inside cells, since this seemed likely to help explain the enzyme’s remarkable but mysterious influence over diverse cellular growth processes. Sabatini proudly projected a slide with the team’s findings, showing the enzyme arrayed along the surface of the organelles called lysosomes.

The audience was dubious. “People literally got up and said, ‘David, that’s the trash bin of the cell. It doesn’t make sense. Why decorate the outside of a trash can?” Sabatini recalled.

Over the nine years since Sabatini’s talk, lysosomes have won more respect. Research continues to show that lysosomes transcend the trash can role, acting as crucial advisers to the nucleus in its job of genetic regulation. That leap in status was obvious at the fourth Gordon Research Conference on Lysosomal Diseases, held March 5-10 in Barga, Italy. The lysosome was also celebrated in a paper that appeared last October in Annual Reviews of Cell and Developmental Biology, “The Lysosome as a Regulatory Hub.” Its authors, the San Francisco Bay Area researchers Rushika Perera and Roberto Zoncu, observed that recent studies have “raised the status of the lysosome from a catabolic dead end to a key signaling node, with far-reaching implications for our understanding of the logic of metabolic regulation both in health and in disease.”

In this loftier reckoning of lysosomes, the organelles deftly integrate metabolic information from throughout the cell and communicate it to the nucleus. Like snooping garbage collectors who learn the secrets of all the homeowners on their route, lysosomes gain a uniquely informed perspective on a cell’s status by picking through its molecular discards. And some of the finely tuned genetic controls of the nucleus would possibly be pilotless without them.

Lysosomes first drew attention in the 1950s, when the Belgian biochemist Christian de Duve stumbled across the saclike intracellular structures while trying to purify a protein found in rat livers. He named the previously unknown sacs after the Greek for “digestive body” because their contents were highly acidic and filled with enzymes that break down virtually any biomolecule that’s set before them. De Duve received a Nobel Prize for his discovery in 1974, but biologists were unenthusiastic about the organelle. Researchers nicknamed the lysosome “the recycle bin of the cell, or the trash can — nothing interesting,” said Zoncu, a biochemist at the University of California, Berkeley.

It wasn’t that lysosomes didn’t seem important — waste disposal systems inevitably are. They are responsible for digesting a cell’s damaged, malformed, superfluous or otherwise undesirable proteins and organelles, along with excess sugars and fats. When genetic defects cause lysosomes to make too little of any of the 60 or more enzymes associated with them, waste products pile up inside cells and cause lysosomal storage diseases, such as Tay-Sachs, Niemann-Pick and other disorders. Moreover, as a series of experiments led by Yoshinori Ohsumi (first at the University of Tokyo, then at Japan’s National Institute for Basic Biology) demonstrated in the 1990s, lysosomes are also instrumental in the vital process of autophagy, which allows cells to cannibalize their own organelles for resources in times of need and to combat the effects of illness and aging. That work brought Ohsumi a Nobel Prize in 2016 — a second Nobel to be awarded for work involving the cell’s lowly trash can.

But in the 1980s, when Andrea Ballabio, the founder of the Telethon Institute of Genetics and Medicine in Naples, was starting out in biological research, studies of the lysosome focused almost exclusively on what goes on inside it. He recalls the field as heavily and narrowly disease driven: Lysosome investigators purified enzymes that were deficient or dysfunctional in specific lysosomal storage disorders.

Continue reading.

Written by Leisureguy

25 April 2017 at 4:17 pm

Posted in Evolution, Science

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